This invention relates to a drug composition with a controlled drug release rate, which makes use of a particular matrix as a carrier.
From the standpoint of exhibition of drug efficacy and a reduction in side effects, it is preferred for a drug to remain at a target site only for the length of time and in the quantity necessary. Research is therefore under way on systems whereby certain specific substances are used as carriers for drugs, the drugs being released only in the quantity and for the length of time necessary.
For example, hyaluronic acid is a polysaccharide which is found in the living body. It has been studied for its physiological activities and also as a carrier for other drugs. Conventionally-known examples of drug release systems ma king use of hyaluronic acid as a carrier can include one containing a physiologically-active peptide in an aqueous solution of hyaluronic acid (JP kokai 2-213), those making use of hyaluronic acid crosslinked with an epoxy compound, divinyl sulfone, a carbodiimide or the like (JP kokai 61-138601, JP kokai 60-233101, JP kokai 5-140201, and JP kokai 7-102002), a sustained release composition of hyaluronic acid and alginic acid (JP kokai 6-100468), a polyion complex of hyaluronic acid and a cationic polyacrylic acid derivative (JP kokai 7-33682), and one making use of a hyaluronic acid derivative (JP kokai 5-255124).
However, the techniques of JP kokai 2-213 and JP kokai 6-100468 have a problem in that they are not sufficiently effective in controlling a drug release rate. The techniques of JP kokai 61-138601, JP kokai 60-233101, JP kokai 5-140201 and JP kokai 7-102002 are accompanied by a problem in that the crosslinking materials have low compatibility with the living body and have no biodegradability. The technique of JP kokai 7-33682 involves a problem in that the cationic polyacrylic acid derivative does not have biodegradability. Further, the technique of JP kokai 5-255124 has problems in that substantial time is required for preparation into a unit dosage form and the release rate of a drug is hardly controllable.
An object of the present invention is to provide a drug composition which has biodegradability and biocompatibility, permits easy control of a drug release rate, and can persistently exhibit its pharmacological effect over a long time.
With a view to achieving the above-described object, the present inventors have therefore proceeded with extensive research. As a result, it has been found that a drug composition with a drug incorporated in a matrix, which has been formed from a biodegradable, biocompatible high molecular substance and/or polyvalent metal ions or polyvalent metal ion source and hyaluronic acid, has biocompatibility and biodegradability and permits free control of the release rate of the drug, leading to the completion of the present invention.
The present invention therefore provides a drug composition with a controlled drug release rate, which comprises:
a matrix formed of the following ingredients (a) and (b):
(a) a biodegradable, biocompatible high-molecular substance and/or polyvalent metal ions or polyvalent metal ion source, and
(b) hyaluronic acid or a salt thereof; and
a drug incorporated as an ingredient (c) in said matrix.